Clinical Trials Register

Summary
EudraCT Number:	2017-003960-11
Sponsor's Protocol Code Number:	CRTH258B2302
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-06-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2017-003960-11

A.3

Full title of the trial

A Two-Year, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Adult Patients with Visual Impairment due to Diabetic Macular Edema (KITE)

Dvojročné randomizované, dvojito maskované multicentrické klinické skúšanie fázy III v dvoch skupinách na zhodnotenie účinnosti a bezpečnosti brolucizumabu v porovnaní s afliberceptom u dospelých pacientov s poruchou zraku v dôsledku diabetického edému makuly (KITE)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Phase III Study Assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Adult Patients with Visual Impairment due to Diabetic Macular Edema

A.4.1

Sponsor's protocol code number

CRTH258B2302

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Slovakia s.r.o.
B.5.2	Functional name of contact point	DRA information desk
B.5.3	Address:
B.5.3.1	Street Address	Galvaniho 15/A
B.5.3.2	Town/ city	Bratislava
B.5.3.3	Post code	821 04
B.5.3.4	Country	Slovakia
B.5.4	Telephone number	+421 2 50706116
B.5.5	Fax number	+421 2 50706100
B.5.6	E-mail	dra.slovakia@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Beovu
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BROLUCIZUMAB
D.3.9.1	CAS number	1531589-13-5
D.3.9.2	Current sponsor code	RTH258 / ESBA1008
D.3.9.3	Other descriptive name	Anti-VEGF monoclonal antibody
D.3.9.4	EV Substance Code	SUB180753
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Eylea
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	aflibercept
D.3.9.1	CAS number	862111-32-8
D.3.9.3	Other descriptive name	AFLIBERCEPT
D.3.9.4	EV Substance Code	SUB26987
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

diabetic macular edema

E.1.1.1

Medical condition in easily understood language

diabetic macular edema

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10057934
E.1.2	Term	Diabetic macular edema
E.1.2	System Organ Class	100000004853

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the visual outcome after the first year of treatment

E.2.2

Secondary objectives of the trial

To
•demonstrate that brolucizumab is non-inferior to aflibercept with respect to visual outcome during the last 3 months of the first year of treatment
•estimate the proportion of patients treated at q12w frequency with brolucizumab
•estimate the predictive value of the first q12w cycle for maintenance of q12w treatment with brolucizumab
•assess the potential to extend treatment intervals for brolucizumab patients during the second year of treatment
•evaluate the functional and anatomical outcome with brolucizumab relative to aflibercept
•evaluate the effect of brolucizumab relative to aflibercept on the DR status
•assess the safety of brolucizumab relative to aflibercept
•evaluate the effect of brolucizumab relative to aflibercept on patient-reported outcomes (VFQ-25)
•confirm the systemic brolucizumab exposure in patients with visual impairment due to DME
•assess the immunogenicity of brolucizumab/aflibercept over two years of treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

General
1.Patients must give written informed consent before any study related assessments are performed
2.Patients ≥18 years of age at baseline
3.Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening
4.Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study
Study Eye
5.Visual impairment due to DME with:
•BCVA score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320), at screening and baseline
•DME involving the center of the macula, with central subfield retinal thickness (measured from RPE to ILM inclusively) of ≥320 µm on SD-OCT at screening
If both eyes are eligible, the eye with the worse visual acuity will be selected for study eye. However, the investigator may select the eye with better visual acuity, based on medical reasons or local ethical requirements.

E.4

Principal exclusion criteria

1.Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye
2.Active proliferative diabetic retinopathy in the study eye as per the investigator
3.Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g., cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
4.Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
5.Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
6.Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication or according to investigator’s judgment, at screening or baseline
7.Neovascularization of the iris in the study eye at screening or baseline
8.Evidence of vitreomacular traction in the study eye at screening or baseline which, in the opinion of the investigator, affect visual acuity

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in BCVA at Week 52

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

E.5.2

Secondary end point(s)

•Change from baseline in BCVA averaged over a period Week 40 to Week 52
•Proportion of patients maintained at q12w up to Weeks 52 & 100
•Proportion of patients maintained at q12w up to Week 52, within those patients that qualified for q12w at Week 36
•Proportion of patients maintained at q12w/q16w up to Week 100, within those patients that qualified for q12w at Week 36
•Proportion of patients maintained on q16w up to Week 100 within the patients on q12w at Week 68 and on q16w at Week 76
•Proportion of patients re-assigned and maintained on q12w up to Week 100 within the patients on q8w at Week 68 and on q12w at Week 80
•Treatment status at Week 100
•Change from baseline by visit up to Week 100 in BCVA and in parameters derived from SD-OCT, Color fundus photography and Fluorescein angiography
•Change in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score up to Week 100
•Incidence of Ocular and Non-ocular AEs, vital signs and laboratory values up to Week 100
•Change in patient reported outcomes (VFQ-25) total and subscale scores from baseline up to Week 100
•Systemic brolucizumab concentration approximately 24 hours after initial and final loading phase doses
•ADA status at baseline and up to Week 100

E.5.2.1

Timepoint(s) of evaluation of this end point

@ weeks 40, 52 and/or 100

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Bulgaria

Czech Republic

Denmark

Estonia

France

Germany

Hungary

India

Korea, Republic of

Latvia

Lebanon

Lithuania

Malaysia

Norway

Poland

Russian Federation

Singapore

Slovakia

Sweden

Switzerland

Taiwan

Turkey

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

267

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

226

F.4.2.2

In the whole clinical trial

356

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

A patient will be considered to have completed the study when the patient has completed the last visit planned in the protocol.
The investigator and/or referring physician will recommend the appropriate follow-up medical care, if needed, for all patients who are prematurely withdrawn from the study.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-06-08

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials